Lung Adenocarcinoma Distally Rewires Hepatic Circadian Homeostasis
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nihms780858.pdf
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Author(s)
Masri, Selma
Kinouchi, Kenichiro
Liu, Yu
Cervantes, Marlene
Baldi, Pierre
Sassone-Corsi, Paolo
Papagiannakopoulos, Thales
Jacks, Tyler E.
Date Issued
June 25, 2018
Journal
Cell
Publisher
Elsevier
Citation
Masri, Selma et al. “Lung Adenocarcinoma Distally Rewires Hepatic Circadian Homeostasis.” Cell 165, 4 (May 2016): 896–909 © 2016 Elsevier Inc
Version
Author's final manuscript
Abstract
The circadian clock controls metabolic and physiological processes through finely tuned molecular mechanisms. The clock is remarkably plastic and adapts to exogenous "zeitgebers," such as light and nutrition. How a pathological condition in a given tissue influences systemic circadian homeostasis in other tissues remains an unanswered question of conceptual and biomedical importance. Here, we show that lung adenocarcinoma operates as an endogenous reorganizer of circadian metabolism. High-throughput transcriptomics and metabolomics revealed unique signatures of transcripts and metabolites cycling exclusively in livers of tumor-bearing mice. Remarkably, lung cancer has no effect on the core clock but rather reprograms hepatic metabolism through altered pro-inflammatory response via the STAT3-Socs3 pathway. This results in disruption of AKT, AMPK, and SREBP signaling, leading to altered insulin, glucose, and lipid metabolism. Thus, lung adenocarcinoma functions as a potent endogenous circadian organizer (ECO), which rewires the pathophysiological dimension of a distal tissue such as the liver.
MIT Department
Massachusetts Institute of Technology. Division of Comparative Medicine
Howard Hughes Medical Institute
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Creative Commons Attribution-NonCommercial-NoDerivs License
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DOI of Published Version
https://doi.org/10.1016/J.CELL.2016.04.039
